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Background: Biallelic variants in POLR1C are associated with POLR3-related leukodystrophy (POLR3-HLD), or 4H leukodystrophy (Hypomyelination, Hypodontia, Hypogonadotropic Hypogonadism), and Treacher Collins syndrome (TCS). The clinical spectrum of POLR3-HLD caused by variants in this gene has not been described. Methods: A cross-sectional observational study involving 25 centers worldwide was conducted between 2016 and 2018. The clinical, radiologic and molecular features of 23 unreported and previously reported cases of POLR3-HLD caused by POLR1C variants were reviewed. Results: Most participants presented between birth and age 6 years with motor difficulties. Neurological deterioration was seen during childhood, suggesting a more severe phenotype than previously described. The dental, ocular and endocrine features often seen in POLR3-HLD were not invariably present. Five patients (22%) had a combination of hypomyelinating leukodystrophy and abnormal craniofacial development, including one individual with clear TCS features. Several cases did not exhibit all the typical radiologic characteristics of POLR3-HLD. A total of 29 different pathogenic variants in POLR1C were identified, including 13 new disease-causing variants. Conclusions: Based on the largest cohort of patients to date, these results suggest novel characteristics of POLR1C-related disorder, with a spectrum of clinical involvement characterized by hypomyelinating leukodystrophy with or without abnormal craniofacial development reminiscent of TCS.
Obstructive sleep apnoea is a common chronic sleep disorder characterised by collapse of the upper airway during sleep. The nasal airway forms a significant part of the upper airway and any obstruction is thought to have an impact on obstructive sleep apnoea. A systematic review was performed to determine the role of rhinological surgical interventions in the management of obstructive sleep apnoea.
A systematic review of current literature was undertaken; studies were included if they involved comparison of a non-surgical and/or non-rhinological surgical intervention with a rhinological surgical intervention for treatment of obstructive sleep apnoea.
Sixteen studies met the selection criteria. The pooled data suggest that there are reductions in the apnoea/hypopnea index and respiratory disturbance index following nasal surgery. However, the current body of studies is too heterogeneous for statistically significant meta-analysis to be conducted.
Nasal surgery may have limited benefit for a subset of patients based on current evidence.
Background: The role of extent of surgical resection (EOR) on clinical outcomes in patients with low-grade glioma requires further examination. Methods: We systematically searched MEDLINE, Embase, and the Cochrane Library for studies published between January 1, 1990 and January 5, 2018 on predefined patient outcomes regarding different EOR of low-grade glioma. Results: Our literature search yielded 60 studies including 13,289 patients. Pooled estimates of overall survival showed an increase from 3.79 years (95% CI, 2.37–5.22) in the biopsy group to 6.68 years (95% CI, 4.19–9.16) in STR to 10.65 years (95% CI, 6.78–14.52) in GTR. When compared to STR, GTR prolonged progression-free survival by 2.08 years (95% CI, 0.26–3.89; P=0.025). Pooled estimates of seizure control showed an improvement from 47.8% (95% CI, 26.7–69.6) with biopsy to 54.2% (95% CI, 48.7–59.6) with STR to 81.0% (95% CI, 74.6–86.2) with GTR. Compared to STR, GTR delayed malignant transformation (RR, 0.43; 95% CI, 0.20–0.93; P=0.032), without increasing postoperative mortality (RR, 0.38; 95% CI, 0.07–1.97; P=0.250) or morbidity (RR, 1.22; 95% CI, 0.65–2.28; P=0.540). Conclusions: Among patients with low grade gliomas, higher degrees of safe EOR, were associated with longer overall and progression-free survival, better seizure control, and delayed malignant transformation, without increased mortality or morbidity.
Rice has the lowest grain protein content (GPC) among cereals. Efforts have been made to improve GPC through the modified bulk-pedigree method of selection. A total of 1780 F8 recombinant lines were derived in the year 2013 from five different cross combinations involving two high-GPC landraces, namely ARC10075 and ARC10063, three high-yielding parents, namely Swarna, Naveen and IR64, and one parent, namely Sharbati, known for superior grain quality with high micronutrient content. Near-infrared spectroscopy was used to facilitate high-throughput selection for GPC. Significant selection differential, response to selection and non-significant differences between the predicted and observed response to selection for GPC and protein yield indicated the effectiveness of this selection process. This resulted in lines with high GPC, protein yield and desirable levels of amylose content. Further, based on high mean and stability for GPC and protein yield over the environments in the wet seasons of 2013, 2014 and the dry season of 2014, 12 elite lines were identified. Higher accumulation of glutelin fraction and non-significant change in prolamin/glutelin ratio in the grain suggested safe guarding of the nutritional value of rice grain protein of most of these identified lines. Since rice is the staple food of millions, the output of breeding for high GPC could have a significant role in alleviating protein malnutrition, especially in the developing world.
There is lack of evidence on the differential impact of maternal macronutrient consumption: carbohydrates (CHO), fats and protein on birth weight. We investigated the association between maternal dietary macronutrient intakes and their sub-components such as saccharides and fatty acids and birth weight. This analyses included 1,196 women with singleton pregnancies who were part of the CAffeine and REproductive health study in Leeds, UK between 2003 and 2006. Women were interviewed in each trimester. Dietary information was collected twice using a 24-h dietary recall about 8–12 weeks and 13–27 weeks of gestation. Multiple linear regression models adjusted for alcohol and smoking in trimester 1, showed that each additional 10 g/d CHO consumption was associated with an increase of 4 g (95 % CI 1, 7; P=0·003) in birth weight. Conversely, an additional 10 g/d fat intake was associated with a lower birth weight of 8 g (95 % CI 0, 16; P=0·04) when we accounted for energy contributing macronutrients in each model, and maternal height, weight, parity, ethnicity, gestational age at delivery and sex of the baby. There was no evidence of an association between protein intake and birth weight. Maternal diet in trimester 2 suggested that higher intakes of glucose (10 g/d) and lactose (1 g/d) were both associated with higher birth weight of 52 g (95 % CI 4, 100; P=0·03) and 5 g (95 % CI 2, 7; P<0·001) respectively. These results show that dietary macronutrient composition during pregnancy is associated with birth weight outcomes. An appropriately balanced intake of dietary CHO and fat during pregnancy could support optimum birth weight.
To describe our experience and provide guidelines for maximum safe balloon sizes according to age in children undergoing balloon dilatation.
A retrospective review was conducted of children undergoing balloon dilatation for subglottic stenosis in a paediatric tertiary unit between May 2006 and February 2016.
A total of 166 patients underwent balloon dilatation. Mean ( ± standard deviation) patient age was 4.5 ± 3.99 years. The median balloon size was 8 mm, the median balloon inflation pressure was 10 atm, and the mean balloon inflation time was 65.1 ± 18.6 seconds. No significant unexpected events occurred. The Pearson correlation co-efficient for the relationship between patient age and balloon size was 0.85 (p = 0.001), suggesting a strongly positive correlation.
This study demonstrated that balloon dilatation is a safe procedure for airway stenosis. The results suggest using a balloon diameter that is equal to the outer diameter of the age-appropriate endotracheal tube +1 mm for the larynx and subglottis and +2 mm for the trachea.
In low- and middle-income countries, mental health training often includes sending few generalist clinicians to specialist-led programs for several weeks. Our objective is to develop and test a video-assisted training model addressing the shortcomings of traditional programs that affect scalability: failing to train all clinicians, disrupting clinical services, and depending on specialists.
We implemented the program -video lectures and on-site skills training- for all clinicians at a rural Nepali hospital. We used Wilcoxon signed-rank tests to evaluate pre- and post-test change in knowledge (diagnostic criteria, differential diagnosis, and appropriate treatment). We used a series of ‘Yes’ or ‘No’ questions to assess attitudes about mental illness, and utilized exact McNemar's test to analyze the proportions of participants who held a specific belief before and after the training. We assessed acceptability and feasibility through key informant interviews and structured feedback.
For each topic except depression, there was a statistically significant increase (Δ) in median scores on knowledge questionnaires: Acute Stress Reaction (Δ = 20, p = 0.03), Depression (Δ = 11, p = 0.12), Grief (Δ = 40, p < 0.01), Psychosis (Δ = 22, p = 0.01), and post-traumatic stress disorder (Δ = 20, p = 0.01). The training received high ratings; key informants shared examples and views about the training's positive impact and complementary nature of the program's components.
Video lectures and on-site skills training can address the limitations of a conventional training model while being acceptable, feasible, and impactful toward improving knowledge and attitudes of the participants.
The State of Qatar experienced a sandstorm on the night of April 1, 2015, lasting approximately 12 hours, with winds of more than 100 km/h and average particulate matter of approximately 10 μm in diameter. The emergency department (ED) of the main tertiary hospital in Qatar managed 62% of the total emergency calls and those of higher triage order. The peak load of patients during the event manifested approximately 6 hours after the onset. The Major Emergency Command Centre of the hospital ensured the department was maximally organized in terms of disaster management, and established protocols were brought into action. Multiple timely meetings were convened in efforts to effectively execute plans that included rapid emergency medical services handover time, resourcing staff, maximizing bed space, preventing dust entry in the ED, bypassing certain administrative processes, canceling day-surgeries that did not affect inpatient morbidity, and procuring additional respiratory equipment. Patients arrived mainly with exacerbations of asthma and respiratory distress, ophthalmic emergencies, and vehicular trauma; surprisingly, the incidence of pedestrian injuries did not vary. (Disaster Med Public Health Preparedness. 2017;11:227–238)
A novel reduced-order model for time-varying nonlinear flows arising from a resolvent decomposition based on the time-mean flow is proposed. The inputs required for the model are the mean-flow field and a small set of velocity time-series data obtained at isolated measurement points, which are used to fix relevant frequencies, amplitudes and phases of a limited number of resolvent modes that, together with the mean flow, constitute the reduced-order model. The technique is applied to derive a model for the unsteady three-dimensional flow in a lid-driven cavity at a Reynolds number of 1200 that is based on the two-dimensional mean flow, three resolvent modes selected at the most active spanwise wavenumber, and either one or two velocity probe signals. The least-squares full-field error of the reconstructed velocity obtained using the model and two point velocity probes is of the order of 5 % of the lid velocity, and the dynamical behaviour of the reconstructed flow is qualitatively similar to that of the complete flow.
Background: NMDA receptor encephalitis (NMDARE) is associated with pre-existing psychiatric symptoms and seizure disorders. It is not typically associated with elevated ICP. Diagnostically, EEG findings in NMDARE are characteristic as are the pathological features of ovarian teratomas associated with this disease. We report a patient who tested positive for NMDARE however presented with features not known to be associated with the disease including elevated ICP, atypical EEG findings and grossly atypical features on pathological section. Results: A 26 year old woman presented with psychiatric symptoms and status epilepticus. On examination, she was found to have papilledema and eleveated ICP on measurement. Her imaging and EEG demonstrated atypical findings, not consistent with NMDARE. CT scan of the abdomen demonstrated an adnexal mass. CSF studies eventually tested positive for NMDARE and following removal of her ovarian teratoma, the pathology demonstrated atypical findings for lesions associated with NMDARE classically. Conclusions: NMDARE is a new entity, which has historically shown a typical clinical course. Our case demonstrates a previously undescribed presentation of NMDARE with elevated ICP, atypical EEG findings and unique pathology of the associated ovarian teratoma.
The effect of streamwise-varying steady transpiration on turbulent pipe flow is examined using direct numerical simulation at fixed friction Reynolds number
. The streamwise momentum equation reveals three physical mechanisms caused by transpiration acting in the flow: modification of Reynolds shear stress, steady streaming and generation of non-zero mean streamwise gradients. The influence of these mechanisms has been examined by means of a parameter sweep involving transpiration amplitude and wavelength. The observed trends have permitted identification of wall transpiration configurations able to reduce or increase the overall flow rate
, respectively. Energetics associated with these modifications are presented. A novel resolvent formulation has been developed to investigate the dynamics of pipe flows with a constant cross-section but with time-mean spatial periodicity induced by changes in boundary conditions. This formulation, based on a triple decomposition, paves the way for understanding turbulence in such flows using only the mean velocity profile. Resolvent analysis based on the time-mean flow and dynamic mode decomposition based on simulation data snapshots have both been used to obtain a description of the reorganization of the flow structures caused by the transpiration. We show that the pipe flows dynamics are dominated by a critical-layer mechanism and the waviness induced in the flow structures plays a role on the streamwise momentum balance by generating additional terms.
The binary X-ray source GX 1 + 4 was observed during a balloon flight in 1986, November. The source was in a relatively high intensity state. Time analysis of the data shows that the pulsation period was 111.8 ± 1.0 s indicating that one or more episodes of spin-down occurred between 1980 and 1986. Folded pulse profiles are very broad with an indication of a notch at the peak. Evidence has been found for a correlation between hard X-ray intensity and phase of the proposed 304 day orbital period. The time averaged intensity since 1980 is an order of magnitude lower than during the 1970’s. A survey of the post 1980 data shows that several reversals of the period derivative have occurred. Spin-up at the rates typical of the 1970’s has been followed by a dramatic spin-down episode with dP/dt>2.4 × 10−7 s/s.
To investigate the assessment and management of paediatric snoring and obstructive sleep apnoea in UK otolaryngology departments.
A telephone questionnaire survey of UK otolaryngology departments was conducted over a 16-week period.
The response rate was 61 per cent (85 out of 139 trusts). Use of pre-operative pulse oximetry was reported by 84 per cent of respondents, mainly to diagnose obstructive sleep apnoea (73 per cent) or stratify post-operative risk (46 per cent). Thirty-one per cent of respondents reported using post-operative pulse oximetry. Twenty-five per cent of respondents have a dedicated management protocol for paediatric obstructive sleep apnoea and snoring. Thirty-four per cent require prior clinical commissioning group approval before performing surgery. Fifty-eight per cent of respondents reported following up their obstructive sleep apnoea patients after surgery. The mean follow-up period (±standard deviation) was 6.8 ± 1.2 weeks.
There is variation in the assessment and management of paediatric snoring and obstructive sleep apnoea across the UK, particularly in the use of pre- and post-operative pulse oximetry monitoring, and further guidelines regarding this are necessary.
Lower and middle income countries (LMICs) are home to >80% of the global population, but mental health researchers and LMIC investigator led publications are concentrated in 10% of LMICs. Increasing research and research outputs, such as in the form of peer reviewed publications, require increased capacity building (CB) opportunities in LMICs. The National Institute of Mental Health (NIMH) initiative, Collaborative Hubs for International Research on Mental Health reaches across five regional ‘hubs’ established in LMICs, to provide training and support for emerging researchers through hub-specific CB activities. This paper describes the range of CB activities, the process of monitoring, and the early outcomes of CB activities conducted by the five research hubs.
The indicators used to describe the nature, the monitoring, and the early outcomes of CB activities were developed collectively by the members of an inter-hub CB workgroup representing all five hubs. These indicators included but were not limited to courses, publications, and grants.
Results for all indicators demonstrate a wide range of feasible CB activities. The five hubs were successful in providing at least one and the majority several courses; 13 CB recipient-led articles were accepted for publication; and nine grant applications were successful.
The hubs were successful in providing CB recipients with a wide range of CB activities. The challenge remains to ensure ongoing CB of mental health researchers in LMICs, and in particular, to sustain the CB efforts of the five hubs after the termination of NIMH funding.
This paper presents modifications to powered endoscopic dacryocystorhinostomy without stenting for the management of acquired nasolacrimal duct obstruction.
A retrospective, non-randomised review.
A total of 105 patients with epiphora secondary to acquired nasolacrimal duct obstruction were operated on by our modified powered endoscopic dacryocystorhinostomy approach.
Of 105 patients, 100 (95.2 per cent) have remained asymptomatic. One patient with a narrow ostium had improved symptoms, while four patients continued to experience persistent symptoms (treatment failures).
The modified powered endoscopic dacryocystorhinostomy approach led to excellent results, without bone exposure and granulations, and with early mucosalisation.
This study assessed the use of pulse oximetry testing in children with suspected obstructive sleep apnoea in a hospital setting.
A retrospective review of patients who underwent pulse oximetry testing between April 2013 and October 2013 was performed. Primary outcome measures included positive pulse oximetry results, defined as a McGill oximetry score of 2–4.
Thirty-seven test results were usable for analysis: from 21 pre- and 16 post-operative tests. Only four patients had positive test results. There was a significant difference between pre- and post-operative quality of life outcome scores in the surgical group (p < 0.0001).
Pre-operative pulse oximetry should be used as a guide to help triage patients who require specialist paediatric services, such as a paediatric intensive care unit. The use of pulse oximetry, particularly in the post-operative setting, is unlikely to change patient management and can incur unnecessary financial costs to UK National Health Service Hospital Trusts.
Aspiration pneumonia is an important cause of death in head and neck cancer patients. This study therefore aimed to evaluate the risk factors associated with aspiration pneumonia in head and neck cancer patients.
Hospital death records from 12 years (2000–2012) were reviewed to obtain the number of deaths. Treatment details and cause of death were analysed. Statistical analysis was performed to identify the risk factors for aspiration pneumonia.
The records revealed that aspiration pneumonia was the cause of death in 51 out of 85 patients. Primary tumour site (oropharynx and hypopharynx, odds ratio 3.3; 95 per cent confidence interval 1.17–9.4, p = 0.02) and advanced tumour stage (odds ratio 4.2, 95 per cent confidence interval 1.16–15.61, p = 0.02) had significant negative impacts on aspiration pneumonia related mortality.
Advanced pharyngeal cancer patients are at an increased risk of aspiration pneumonia related death. Investigations for the early detection of this condition are recommended in these high-risk patients.
This paper extends the resolvent formulation proposed by McKeon & Sharma (J. Fluid Mech., vol. 658, 2010, pp. 336–382) to consider turbulence–compliant wall interactions. Under this formulation, the turbulent velocity field is expressed as a linear superposition of propagating modes, identified via a gain-based decomposition of the Navier–Stokes equations. Compliant surfaces, modelled as a complex wall admittance linking pressure and velocity, affect the gain and structure of these modes. With minimal computation, this framework accurately predicts the emergence of the quasi-two-dimensional propagating waves observed in recent direct numerical simulations. Further, the analysis also enables the rational design of compliant surfaces, with properties optimized to suppress flow structures energetic in wall turbulence. It is shown that walls with unphysical negative damping are required to interact favourably with modes resembling the energetic near-wall cycle, which could explain why previous studies have met with limited success. Positive-damping walls are effective for modes resembling the so-called very-large-scale motions, indicating that compliant surfaces may be better suited for application at higher Reynolds number. Unfortunately, walls that suppress structures energetic in natural turbulence are also predicted to have detrimental effects elsewhere in spectral space. Consistent with previous experiments and simulations, slow-moving spanwise-constant structures are particularly susceptible to further amplification. Mitigating these adverse effects will be central to the development of compliant coatings that have a net positive influence on the flow.
Abnormalities in the anterior inter-hemispheric connectivity have previously been implicated in major depressive disorder. Disruptions in fractional anisotropy in the callosum and fornix have been reported in schizophrenia and major depressive disorder. Oligodendrocyte density and overall size of the callosum and fornix show no alteration in either illness, suggesting that gross morphology is unchanged but more subtle organizational disruption may exist within these brain regions in mood and affective disorders.
Using high-resolution oil-immersion microscopy we examined the cross-sectional area of the nerve fibre and the axonal myelin sheath, and using standard high-resolution light microscopy we measured the density of myelinated axons. These measurements were made in the genu of the corpus callosum and the medial body of the fornix at its most dorsal point. Measures were taken in the sagittal plane in the callosal genu and in the coronal plane at the most dorsal part of the fornix body.
Cases of major depressive disorder had significantly greater mean myelin cross-sectional area (p = 0.017) and myelin thickness (p = 0.004) per axon in the genu than in control or schizophrenia groups. There was no significant change in the density of myelinated axons, and no changes observed in the fornix.
The results suggest a clear increase of myelin in the axons of the callosal genu in MDD, although this type of neuropathological study is unable to clarify whether this is caused by changes during life or has a developmental origin.
To explore the treatment outcomes of patients treated with re-irradiation for recurrent or second primary head and neck cancer.
An analysis was performed of 79 head and neck cancer patients who underwent re-irradiation for second primaries or recurrent disease from January 1999 to December 2011.
Median time from previous radiation to re-irradiation for second primary or recurrence was 53.6 months (range, 2.7–454.7 months). Median age at diagnosis of first primary was 54 years. Median re-irradiation dose was 45 Gy (range, 45–60 Gy). Acute grade 3 or worse toxicity was seen in 30 per cent of patients. Median progression-free survival for recurrent disease was 15.0 months (95 per cent confidence interval, 8.33–21.66). The following factors had a statistically significant, positive impact on progression-free survival: patient age of less than 50 years (median progression-free survival was 29.43, vs 13.9 months for those aged 50 years or older; p = 0.004) and disease-free interval of 2 years or more (median progression-free survival was 51.66, vs 13.9 months for those with less than 2 years disease-free interval).
Re-irradiation of second primaries or recurrences of head and neck cancers with moderate radiation doses yields acceptable progression-free survival and morbidity rates.